GENE AND VIRUS THERAPY PROGRAM PROJECT SUMMARY The Gene and Virus Therapy Program (GVT) is currently comprised of 22 accomplished members, both basic scientists and clinician investigators from 10 departments and divisions working interactively to create novel gene transfer, virotherapy and immunovirotherapy approaches for the treatment of cancer. This goal is supported by 4 specific aims: 1) To develop novel gene and virus platforms for use in cancer therapy; 2) To develop cancer immunotherapies by exploring the immunomodulatory potential of gene- and virus-based therapeutics; 3) To assess preclinical, clinical, pharmacologic, and immunologic properties of vectors used in cancer therapy and optimize clinical application, and 4) To evaluate the role of cells as carriers in gene and virus therapy approaches to cancer therapy. In addition to intensive intraprogrammatic interactions, substantive interprogrammatic interactions, essential for the process of clinical translation, have been established between the GVT and other Mayo Clinic Cancer Center (MCCC) Programs including the Hematologic Malignancies Program (HMP), the Women's Cancer Program (WCP), the Gastrointestinal Cancer Program (GI), the Neuro- Oncology Program (NONC) and the Cancer Immunology and Immunotherapy Program (CII). The Leader, Dr. Evanthia Galanis, is an oncologist with considerable stature in the field of gene and virus therapy. Productivity of the Program during the current funding period has been significant, including direct funding of $8.9M (vs $7.2M at the 2013 renewal) and a total of 426 publications (as of 12/31/2017). In addition,multiple Phase I/II clinical trials of recombinant viruses or oncolytic virus infected carrier stem cells which were designed, constructed, preclinically tested, and manufactured at the Mayo Clinic have been launched and/or completed under several program sponsored IND. The efficacy observed with some of these approaches has led to later stage, randomized phase II trials. Additionally, there are several promising projects in the translational pipeline, including immunovirotherapy strategies employing virus strains encoding immunostimulatory transgenes such as MV-NAP in breast cancer, vesicular stomatitis virus libraries in melanoma and combinational strategies with immune checkpoint inhibitors.